This work aimed to evaluate the effect of different dietary levels of Guardizen-M as a probiotic on some blood parameters and histological structure of some internal organs of Nile tilapia. The experimental design was completely randomized; a total number of 180 Nile tilapia with average weight 68±2.66g and total length 15.41±0.27 cm. were reared in 12 floating cages. The fish groups were distributed as four treatments and three replicates; a control group and three Guardizen-M treated groups (1g /kg feed, 2g /kg feed, and 3g /kg feed). All experimental groups were fed the experimental diets at a rate of 3% of the live body weight of the fish. The results of the present work revealed that no significant (P>0.05) differences were recorded in blood parameters except in glucose and alkaline phosphatase. Histological studies of liver and intestine indicated that increase epithelial height of enterocytes lining the intestinal villi with increase in acidic secretion of goblet cells. The intensity of the Periodic acid–Schiff (PAS) staining increased proportionally with the increasing of the concentration of probiotics in treatment groups in comparison to control.  Alkaline phosphatase activity revealed a difference among three experimental groups in comparison to control one. Results of the current study concluded that reversal effect of probiotics considering the proportion of dose. The greater area of hepatic cells increased proportionally with an increasing of the concentration of probiotics and created a greater area of nutrient storage as observed in hepatic cells.